Using new brain imaging techniques, the researchers were able to predict the course of neurodegeneration in Alzheimer’s patients. Ultimately, these discoveries may lead to personalized treatments.
Alzheimer’s disease is the leading cause of dementia worldwide. According to the WHO, 50 million people suffer from it today, and due to the aging of the population, these numbers are unlikely to improve quickly. But today, scientists at the Center for Memory and Aging at the University of San Francisco (UCSF) have made a major breakthrough in this field. Using new brain imaging techniques, they have succeeded in predicting how the nerve cells in the cerebral cortex will disappear during the course of the disease. The results of this research were published in the journal Science Translational Medicine on January 1. In the long term, their discoveries may help to refine the prognosis of patients and personalize treatment.
Alzheimer’s disease is characterized by deposits of amyloid proteins that first form plaques between neurons and then deposits of tau protein in the neurons. For years, researchers have been focusing on the importance of amyloid plaques and developing drugs to address this aspect of the disease. Nowadays, more and more scientists are interested in Tau, which they believe could be an important biological marker of the disease.
“No one doubts that amyloid plays a role in Alzheimer’s disease, but more and more tau findings are beginning to shift how people think about what is actually driving the disease,” says Professor Renaud La Joie, lead author of the new study. “Still, just looking at postmortem brain tissue, it has been hard to prove that tau tangles cause brain degeneration and not the other way around. One of our group’s key goals has been to develop noninvasive brain imaging tools that would let us see whether the location of tau buildup early in the disease predicts later brain degeneration.”
Tau is an important factor in neurodegeneration
During their study, Renaud La Joie and colleagues recruited 32 participants with early clinical Alzheimer’s disease and gave them a positron emission tomography (PET) scan using two different tracers to measure levels of amyloid and tau protein in their brains. The participants also underwent MRI scans to measure the structural integrity of their brains at the beginning of the study and in follow-up examinations one or two years later.
The researchers then found that the total amount of Tau protein in the brains of the participants at the beginning of the study predicted the extent of degeneration 15 months later. In addition, Tau accumulation patterns predicted atrophy at the same sites with an accuracy of more than 40%.
“The fact that Tau accumulation predicts where degeneration will occur supports our hypothesis that Tau is a key factor in neurodegeneration in Alzheimer’s disease,” explains Renaud La Joie.
Very strong predictions
PET scans also showed that younger study participants had higher levels of tau in their brains and a stronger link between initial tau levels and subsequent brain atrophy. Furthermore, other factors, such as other abnormal proteins or vascular lesions, may play a role in the late onset of Alzheimer’s disease.
“The correlation between the spread of tau and what happened to the brain the following year was really striking,” said neurologist Gil Rabinovici, head of the PET imaging program at the UCSF Memory and Aging Center. “PET Tau imaging not only predicted how much atrophy we would see but also where it would occur. These predictions were far more meaningful than anything we could do with any other imaging technique, and they complement the evidence that tau is an important factor in the disease,” he says.
These discoveries could lead to more effective drugs and more personalized care for people with dementia. This is not possible today because of the high variability of the disease from patient to patient.
Giving patients an idea of what to expect.
“One of the first things people want to know when they hear the diagnosis of Alzheimer’s is simply what the future holds for them or their loved ones. Will it be a long memory lapse or a rapid deterioration leading to dementia? How long will the patient be able to live independently? Will he or she lose the ability to speak or to move on his or her own? These are questions that we cannot answer at the moment, except in very general terms,” continues Gil Rabinovici. With this tool, we could now, for the first time, give patients an idea of what to expect by revealing the biological process underlying their disease”.
“The ability to sensitively monitor the accumulation of tau in living patients would for the first time enable clinical researchers to find treatments that could delay or even prevent the specific path of brain atrophy predicted for each patient,” he concludes.
In the US, more than 5.8 million people suffer from Alzheimer’s disease. The disease usually manifests itself through memory impairment, then other brain functions are affected. Gradually, daily tasks become increasingly difficult and it becomes almost impossible for patients to adapt to new situations. Nearly 500,000 new cases of Alzheimer’s or other forms of dementia are diagnosed every year.